Singh L Ravithej, Avula Srinivasa Rao, Raj Sneha, Srivastava Akanksha, Palnati Gopala Reddy, Tripathi C K M, Pasupuleti Mukesh, Sashidhara Koneni V
Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, India.
Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, India.
J Antibiot (Tokyo). 2017 Aug;70(9):954-961. doi: 10.1038/ja.2017.70. Epub 2017 Jun 21.
Molecular hybridization approach is an emerging tool in drug discovery for designing new pharmacophores with biological activity. A novel, new series of coumarin-benzimidazole hybrids were designed, synthesized and evaluated for their broad spectrum antimicrobial activity. Among all the synthesized molecules, compound (E)-3-(2-1H-benzo[d]imidazol-1-yl)-1-((4-chlorobenzyl)oxy)imino)ethyl)-2H-chromen-2-one showed the most promising broad spectrum antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Proteus vulgaris. In addition, it has showed no cytotoxicity and hemolysis at 10 times the MIC concentration. SAR studies indicate that position of the chlorine atom in the hybrid critically determines the antibacterial activity.
分子杂交方法是药物发现中用于设计具有生物活性的新药理学基团的一种新兴工具。设计、合成了一系列新型的香豆素 - 苯并咪唑杂化物，并对其广谱抗菌活性进行了评估。在所有合成的分子中，化合物（E）-3-（2-1H-苯并[d]咪唑-1-基）-1-（（4-氯苄基）氧基）亚氨基）乙基）-2H-色烯-2-酮对铜绿假单胞菌、金黄色葡萄球菌、枯草芽孢杆菌和普通变形杆菌表现出最有前景的广谱抗菌活性。此外，在MIC浓度的10倍时，它没有显示出细胞毒性和溶血作用。构效关系研究表明，杂化物中氯原子的位置对抗菌活性起关键作用。
